Tryptamides modulate protein phosphatase 2A (PP2A) to enhance brain health and its various cognitive functions. Currently tryptamides, more specifically eicosanoyl, docosanoyl and tetracosanoyl 5-hydroxytryptamides, are available for incorporation, in an un-isolated form, in the human diet, as trace amounts may be found in coffee and cocoa products.
More specifically, Robusta coffee beans may contain 565-1120 mg/kg and Arabica coffee beans may contain 500-2370 mg/kg of total tryptamides (Maier, 1981). However, human consumption of coffee can come in form of an aqueous extract providing only 0.6-0.8 mg of total trpytamindes per serving. The total tryptamides can include 13.26% of early eluting tryptamides and 86.74% of late eluting tryptamides with at least 40%, 41% and 3% of eicosanoyl, docosanoyl and tetracosanoyl tryptamides correspondingly.
Eicosanoyl 5-hydroxytryptamide levels in common coffee drinks are shown below in Table 1. Consumption of a serving of a commercial coffee drink can deliver between 0.6 to 0.72 mg of eicosanoyl 5-hydroxytryptamide.
TABLE 1eicosanoyl 5-eicosanoyl 5-hydroxytryptamidehydroxytryptamideServing sizeCoffee Drink(mg/mL)per serving (mg)(mL)Espresso0.0240.7230Regular Coffee0.0040.8200Instant Coffee0.0030.6200
Furthermore, certain diterpenes, such as cafestol and kahweol, found in coffee are associated with promoting elevated cholesterol levels to the subject when administered, showing of at least an 8% increase in men and a 10% increase in women. In fact, coffee contains up to 0.6-1% of diterpenes that translates to 3-7 mg of diterpenes per serving in brewed coffee. Literature papers suggest that each 10 mg of diterpenes consumed per day can elevate serum cholesterol by 5 mg/dL. Therefore, 3-5 servings of coffee a day, which appear to be the minimum needed for the long term neuroprotection, may have some cardiovascular liabilities, particularly in subjects with underlying conditions—such as existing cardiovascular disease, smoking, a sedentary lifestyle and heredity factors—that make them prone to high cholesterol and/or other cardiovascular maladies.
Furthermore, coffee contains significant amounts of caffeine in amounts of 50-436 mg per serving and decaffeinated coffee about 2-25 mg per serving (http://www.cspinet.org/new/cafchart.htm). Caffeine is known to raise blood pressure in those already suffering from hypertension, cause insomnia, gout attack, indigestion, headaches, urinary incontinence, and reduce fertility in women. Caffeine overdose may lead to adverse symptoms, including death, especially in those with underlying medical conditions (http://www.caffeineinformer.com/harmful-effects-of-caffeine).
Similarly, cocoa liquor products contain 40.1 mg/kg of total tryptamides or about 1.6 mg per serving. Unfortunately, the bulk of tryptamides consists of docosanoyl and tetracosanoyl derivatives while cocoa products contain no biologically significant amounts of eicosanoyl 5-hydroxytryptamide, which has proven efficacy in various models of neurodegeneration, Parkinson and Alzheimer diseases.
There remains a need for a composition that includes all the benefits of tryptamides, but without the negative consequences such as elevated cholesterol levels and blood pressure.
There also remains a need for additional therapeutic agents that can protect against excitotoxic cell death. Over 1.7 million individuals, in the United States alone, suffer from traumatic brain injury (TBI) annually (Faul 2010). At risk groups for TBI include but are not limited to soldiers, athletes, car crash victims and domestic violence victims. (Hoge 2008; DeKosky 2010; McKee 2009; Valera 2003). It has been linked to diseases such as chronic traumatic encephalopathy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, motor neuron disease and dementia (Mortimer 1991; Flemming 2000; Goldman 2006; Ben-Shlomo 1997; Chen 2007; Schmidt 2010). Post injury observations have shown glutamate levels increase by 2.8 fold (Faden 1989, Globus, 1995). A downstream effect of excessive glutamate exposure is the over activation of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, NMDA (N-methyl-D-aspartate) receptor, and glutamate receptor leading to in an influx of Ca2+, oxidative stress and cellular damage ultimately resulting in excitotoxic cell death. This type of secondary injury has become a target for disease intervention. For example, memantine a non-toxic, non-phychotomimetic, NMDA receptor antagonist, is neuroprotective and has been used as a treatment for Alzheimer's and Parkinson's disease (Kornhuber 1994; Emre 2010; Merello 1999; Reisberg 2003). Nevertheless, additional therapies would be helpful.
The present invention seeks to address these unmet needs.